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Medline ® Abstract for Reference 122

of 'Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia'

A dramatic fetal outcome following transplacental transfer of dasatinib.
Berveiller P, Andreoli A, Mir O, Anselem O, Delezoide AL, Sauvageon H, Chapuis N, Tsatsaris V
Anticancer Drugs. 2012;23(7):754.
Chronic myeloid leukemia is a chronic myeloproliferative disorder of hematopoietic stem cells that occurs in 10% of cases in women of childbearing age. Treatment is mainly based on tyrosine kinase inhibitors such as imatinib, dasatinib, or nilotinib. However, the maternal and embryofetal safety of these drugs in pregnant women is poorly documented. Here, we report the case of a 23-year-old woman diagnosed with a chronic myeloid leukemia. She was treated with dasatinib while she was diagnosed as being pregnant at 7 weeks of gestation. Obstetric monitoring showed fetal hydrops associated with severe fetal bicytopenia, leading to termination of pregnancy at 16 weeks of gestation. Dasatinib concentrations were 4 ng/ml in maternal plasma (usual concentration), 3 ng/ml in fetal plasma, and 2 ng/ml in amniotic fluid. Fetal karyotype was normal. To our knowledge, this is the first report clearly quantifying the amount of transplacental transfer of dasatinib. Moreover, fetal hematological toxicity (leukopenia and thrombocytopenia), edema, ascites, and pleural effusions described in this case report are well-known side effects of dasatinib in adults. Hence, this case highlights the imputability of dasatinib in this adverse outcome, and clearly questions its safety during pregnancy.
PremUp Foundation, INSERM U, Pharmaceutical and Biological Sciences Faculty, Teaching Hospital Cochin - Saint Vincent de Paul, AP-HP, UniversitéParis Descartes, France. paul.berveiller@inserm.fr